The Effect of Mu Agonist on Seizure in Hippocampus

Choi, Byung Joon; Kim, Jin Suk

Abstract

PURPOSE: Mu agonists can be used in clinical conditions where threr is a risk of hypoxic neurosusceptibility. Fentanyl, one of mu agonists may serve as neuroprotection from brain ischemic injury and protects against some kinds of brain injury and appears to play an important role in the regulation of brain excitability, especially in hippocampus during seizure. We investigated the effects of mu agonists - fentanyl and DAGO([D-Ala2, N- Me-Phe4, Gly-ol]-enkephalin) on electroconvulsive seizures.
METHODS
The study was done with Sprague-Dawley rats(7-30 days), weighting from 20.4 g to 78.7 g. The animal were kept in-groups with mother rat in cages, and had free access to food and tap water. The temperature of the animal room is room temperature. Hippocampal slices were taken. Hippocampal slices were exposed to DAGO. Then, we began to record electrical activity of slices every 10 minutes in artificial cerebrospinal fluid. We observed the frequency and duration of electrical activity.
RESULTS
The mean duration and frequency of fentanyl 50 ng/mL-treated ictal activity was 23.1+/-2.4 seconds and 85.98.1(n=7). These results were significant differences compared with control. The mean duration and frequency in fentanyl 50 ng/mL-treated interictal activity was 518.5+/-64.0 seconds, 132.0+/-14.0(n=5). There were also significant differences in the duration and frequency of onset in fentanyl 50 ng/mL-treated interictal activity compared with control showing interictal activity. The mean duration of latency time of onset in fentanyl 50 ng/mL-treated interictal activity was 143.0+/-11.3 seconds(n=5), and there was a significantly different latency of onset time in fentanyl 50 ng/mL-treated interictal activity compared with control showing interictal activity. The mean duration and frequency of DAGO 1M-treated ictal activity was 12.72.8 seconds and 87.3+/-11.1(n=7). These results were significant differences compared with control. The mean duration and frequency in DAGO 1M-treated interictal activity was 464.6+/-42.5 seconds, 64.2+/-23.0(n=5). There were also significant differences in the duration and frequency of onset in DAGO 1M-treated interictal activity compared with control showing interictal activity. The mean duration of latency time of onset in DAGO 1 microM-treated interictal activity was 28.49.4 seconds(n=5), and there was a significantly different latency of onset time in DAGO 1 microM- treated interictal activity compared with control showing interictal activity.
CONCLUSION
Fentanyl 50 ng/mL showed a decrease of electroconvulsive seizures, so did DAGO 1 microM. These exogenous mu agonists suppress electroconvulsive seizures, and with increased levels of mu agonists, there may be a functional anticonvulsant effect through mu agonists, there may be a functional anticonvulsant effect through mu receptors. Also, these seem to modulate the convulsions. The study suggests that mu agonists may play a role in the pathogenesis of electroconvulsive seizures and shows a positive clue to the relationship between anticonvulsive effects and mu agonists.